As with all mammalian neoplasms, one of the main factors leading to a better outcome or cure is the earliest possible detection. More specifically, if a colorectal cancer (CC) is detected when it is classified as either Dukes' Class A or B, the patient has a nearly 80% chance of 5-year survival while if the CC is detected when it is classified as a Dukes' C or D, the 5-year survival drops to about 40%. Although adjuvant chemotherapy and local radiotherapy have improved outcomes from CC, no specific public health measure is more likely to benefit such patients than an effective early detection test.
Using analyses based on DNA-loss rates it is estimated that approximately 2.times.10.sup.11 epithelial cells are shed from the lining of the colon each day. The development of an effective cytological method for the detection of cells shed from tumors of the large bowel has been a topic of major interest for the past half century. The fact remains that after any type of cytological method, the sample is still contaminated to a great extent by stool and bacteria which greatly hamper diagnosis.
Heretofore, numerous methods of limited sensitivity have been employed in an attempt to detect CC as early as possible. The detection of occult blood in stool, for instance, was first held as a very sensitive marker for CC, but only 5% to 10% of the patients in whom occult blood is detected were ultimately diagnosed with CC (Kolata, Science 229:636, 1985; Bader, Diges Dis Sci 31:43s, 1986; Winawer & Miller, Bull WHO 65:105, 1987; Knight et al., JAMA 261:587, 1989). Other methods in common use for the detection of CC, such as sigmoidoscopy, colonoscopy, and contrast enemas are fairly specific and accurate, but due to their invasive and expensive nature have not been suitable for widespread population screening. More recent cytological methods observed the efficacy of increased filtration and isopycnic centrifugation of the lavage or enema samples in Percoll gradients. These studies demonstrated an improvement in the clarity of the final sample, but the loss of cells during the many steps of the procedure makes the method impractical. The increased numbers of false-negative cases which is the result of not being able to see the lost neoplastically transformed cells limits this method greatly.
The complexity and/or invasiveness of the above mentioned methods require well-trained professionals (at least two one to carry out the test and the other to evaluate the results) throughout the procedure, which makes their use in population screening quite expensive. In addition, with these methods screening a single patient may take between six and eight hours. In the case that immunocytochemistry is also applied, the cytologic tests mentioned above are extended four to six hours (and that is if any cancer cells were left after the multiple previous steps of cell isolation and purification).
It would, of course, be advantageous to provide a composition and method for the early detection of colorectal cancer and other cancers which is not invasive, which is not based on multiple centrifugations that may lead to the death of cells crucial in ascertaining the correct diagnosis, and which is extremely specific to the cells under investigation.